Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals

Abstract

Objective HDL function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic, treated HIV-1 infection. Design Retrospective study of HDL function measured in two ways in HIV-1 infected males with low overall CVD risk and healthy males with no known CVD risk matched by race to the HIV-1 infected participants. Methods We examined patient level factors associated with two different measures of HDL dysfunction: reduced antioxidant function (oxidized HDL, HDLox) and reduced HDL-apoA-I exchange (HAE), a measure of HDL remodeling, in the HIV infected and control men. Multivariable-adjusted linear regression analyses were employed adjusting for false discovery rate (FDR), age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, albumin. Results In multivariate analysis among HIV-1 infected males (n=166) (median age 45 years, CD4 T cell count 505 cells/mm3, 30.1% were viremic), higher BMI, lower apoA-I and lower albumin were among the most notable correlates of higher HDLox and lower HAE (p<0.05). In HIV-1 uninfected participants lower albumin and higher BMI were associated with lower HAE and higher HDLox, respectively (p≤0.05). HDLox was inversely related to HAE in HIV-1 infected individuals (p<0.001). Conclusion Increased HDLox correlates with reduced HAE in chronic HIV-1 infection. Higher BMI, lower apoA-I and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection using two independent methods.

Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein

“…In our prior published studies with cryopreserved HDL, this method was able to demonstrate at least 10% relative differences in HDLox compared to HDL from control groups (without disease e.g. chronic HIV infection) 36,37,38 .…”

“…Higher HDLox values are associated with reduced HDL antioxidant function. The readout of this assay is associated with validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction and associated cardiovascular and metabolic risk phenotypes 19,21,27,32,34,35,36,37,38,39,47 . This method offers a convenient, yet robust tool for examining the role of HDL function in human disease.…”

“…We have shown that this fluorescence-based approach does not have the limitations of prior HDL function assays 27,28 . This assay has been further refined and standardized in our laboratory so that it can reliably be used in large scale human studies even with cryopreserved plasma 32,33,34,35,36,37,38,39,40,41,42 . The readout of this assay is associated with readouts of validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction and associated cardiovascular and metabolic risk phenotypes 32,33,34,35,36,37,38,39 .…”

Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro

“…The work utilized samples from the Center for Clinical AIDS Research and Education HDL function study; a cross-sectional study investigating impaired HDL function among viremic and virologically suppressed HIV + men on stable ART [8]. Sociodemographic and clinical characteristics, and measures of HDL function (HDL ox , HAE %) have been described [8].…”

“…In HIV + ART-treated participants with low CVD risk, the readout from our assay correlated with coronary artery calcium score, carotid intima media thickness (surrogate measures of subclinical atherosclerosis) and macrophage activation [3–5]. Furthermore, impaired HDL antioxidant function (as measured by higher HDL ox ) was associated with impaired HDL remodeling [8] (a CVD-relevant measure of HDL function [9]) using a cell-free assay that measures the ability of HDL to release apoA-I (HDL-apoA-I exchange (HAE)) [9,10]. Thus, use of two independent cell-free assays of HDL activity may more accurately reflect HDL dysfunction in treated HIV + persons.…”